Big Pharma Gone Wild

How Risperdal, a drug meant for treating rare psychiatric disorders, became the seventh best-selling medicine in the world.

The e-mail did not beat around the bush.

"The rationale of this center," Christine Cote, vice president of Janssen's Medical Affairs, wrote about the planned MGH-Johnson & Johnson Center for the Study of Pediatric Psychopathology at Massachusetts General Hospital, "is to generate and disseminate data supporting the use of risperidone in this patient population."

Okaaaaay.

But even as postmortems are performed on the unholy alliance between Massachusetts General Hospital and Johnson & Johnson, which surfaced last year, the drug giant is at it again.

In January, Janssen Pharmaceutica N.V., a unit of Johnson & Johnson, announced it was funding a research venture at Vanderbilt University in Nashville, Tenn., to discover "novel drugs for the treatment of schizophrenia," to be led by Jeffrey Conn, former head of Merck's department of neuroscience.

Of course you can't blame J&J for seeking new academic stomping grounds. Its chief academic cheerleader, Harvard child psychiatrist Joseph Biederman, who headed its center at Mass Gen, has been benched for apparent psychopathology-for-pay schemes under which he increased the diagnosis of pediatric bipolar disorder fortyfold.

Janssen is being sued by Texas, New Mexico and other states for hiding Risperdal dangers, marketing it for unapproved uses, ghostwriting, misleading doctors, falsifying science, kickback schemes and wholesale Medicaid fraud.

And - Risperdal's U.S. patent expired in 2008!

Risperdal (risperidone), an atypical anti-psychotic, may have contributed to the deaths of 31 children since its 1993 approval according to the New York Times - including 11 treated for unapproved uses. It may have squandered millions of tax dollars, but it is a branding success story.

How else do you explain a drug for schizophrenia (1 percent of the population), bipolar disorder (2.5 percent) and autism-related irritability in children 5 to 16 years old (less than 1 percent of kids) becoming the seventh best-selling pharmaceutical in the world in 2007?

Of course, some of Risperdal's success came from the award-winning "Living Nightmares" campaign by London ad agency Junction 11, which used Welsh artist Mark Moran's evocative oil paintings "Dog-Woman," "Witches," "Rotting Flesh and Boiling Rain" - get it? - based on case histories to "own the relapse/prevention space" as art director John Timney put it.

And don't forget the "Prescribe Early" campaign by ad agency Torre Lazur McCann, which used a macabre abandoned wallet, teddy bear and keys on a barren street to "to reposition a drug that was being used too late to achieve its maximum benefits" - look what happens when you wait! - according to Pharma Times magazine.

Nor did the continuing-medical-education courses like "Individualizing ADHD Pharmacotherapy with Disruptive Behavioral Disorders" taught by the J&J-funded Robert L. Findling and referring to Risperdal/risperidone 13 times hurt. Credit was available until 2009.

But most of Risperdal's success comes from the unsung doctors - you know who you are - who extolled the drug for unapproved use in pediatric bipolar disorder, ADHD, depression, "agitated, expansive, grandiose" "psychopathologies" [per Biederman], Alzheimer's, jealousy, "oppositional" disorder, borderline states, assorted neurological diseases, sleep and mood disorders and whatever else would stick to the wall.

Like the doctors who upheld the "long-term safety and effectiveness of risperidone for severe disruptive behaviors in children," on the basis of a one-year study in the Journal of the American Academy of Child and Adolescent Psychiatry in 2005. Hello?

How else could a drug known to cause diabetes, obesity, breasts in men, lactation in women and the very tardive dyskinesia it was supposed to prevent be a first-choice drug in state formularies and on Medicaid protocols? Given to children?

How did it become a preferred nursing home treatment despite a warning label that says it increases death in elderly patients with dementia-related psychosis? Bruce Bowman, a resident of Taylor Park Nursing and Rehabilitation Center in Rhinelander, Wis., died last June after being put on Risperdal, reports the Milwaukee Journal Sentinel.

Nor did the FDA's why-hold-up-a-drug-just-because-it's-dangerous attitude hurt. In 2007, it approved Risperdal for adolescents 13-17 with schizophrenia, and children and adolescents 10-17 with "short-term treatment of bipolar mania associated with manic or mixed episodes of bipolar I disorder" on the basis of two six- to eight-week studies. Barely long enough to need validated parking.

In fact, the FDA was surprised when a panel of drug experts in November unanimously rejected out of hand its routine safety monitoring for Risperdal and related drugs for children.

"I'm a little puzzled about the statement that the label is inadequate," said Dr. Thomas Laughren, director of the agency's division of psychiatry products according to the New York Times. "I'm anxious to hear what more we can do."

How about not approving a drug in the first place?

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Martha Rosenberg is a columnist and cartoonist who frequently writes about the impact of the pharmaceutical, food and gun industries on public health. A former medical copywriter, her work has appeared in The Boston Globe, The San Francisco Chronicle, The Los Angeles Times and The Chicago Tribune, as well as on the BBC and in the original National Lampoon.